Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid - Full Text View

Purpose

This study is being done to find out how much of the drug raltegravir (RGV) gets into cerebrospinal fluid (CSF), compared to how much get into the blood and to find out if normal changes in a certain gene in your body affects how much RGV gets into the CSF.

Condition	Intervention	Phase
HIV Infections	Drug: Raltegravir	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Genetic Predictors of Raltegravir Penetration Into Cerebrospinal Fluid

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Plasma Area-under-the-curve. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
The primary outcome for this study was the ratio of the 4-hour CSF concentration value (ng/mL) to the partial plasma area-under-the-curve 0-4h value (h*ng/mL).

Secondary Outcome Measures:

Penetration of Raltegravir (RGV) Into Cerebrospinal Fluid (CSF) Based on Single Plasma Timepoint. [ Time Frame: Day 7 ] [ Designated as safety issue: No ]
This outcome was the ratio of the 4-hour CSF concentration value (ng/mL) to the 4-hour plasma concentration value (ng/mL).


Enrollment:	40
Study Start Date:	August 2008
Study Completion Date:	August 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Open label oral raltegravir Raltegravir a single 400 mg pill taken orally every 12 hours for a total of 7 days.	Drug: Raltegravir 400mg orally every 12 hours for 7 days Other Name: MK-0518

Detailed Description:

The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier where it limits entry of substrate drugs into the central nervous system. Raltegravir (MK-0158), a new HIV-1 integrase inhibitor and potentially major addition to the therapeutic armamentarium against HIV, is a substrate for P-gp. Studies are warranted to elucidate the relevance of P-gp transport for raltegravir in the central nervous system.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion criteria:

Able to give informed consent.
Negative HIV-1 serology.
At least 18 but no more than 55 years of age.
Body mass index <30.
Estimated creatinine clearance ≥ 50 mL/minute within 30 days prior to study entry.
Within 30 days prior to study entry:
- Absolute neutrophil count ≥ 1,000/mm3.
- Hemoglobin ≥ 12.5 g/dL for males and ≥ 11.5 g/dL for females.
- Platelet count ≥ 100,000/mm3.
- AST, ALT, and total bilirubin within normal range.
- Alkaline phosphatase < or = 1.5 x upper limit of normal.
Female study volunteers of reproductive potential must have a negative serum or urine pregnancy test performed within 30 days before study entry.
Must agree not to participate in a conception process.
Drug transporter gene ABCB1 position 3435 genotype C/C or T/T.

Exclusion criteria:

Use of any medication that is metabolized by CYP3A or UGT1A1.
Anticipated need to take any medication that is metabolized by CYP3A or UGT1A1 during the study.
Active drug use or dependence.
Inability to abstain from alcohol-containing beverages, grapefruit, and grapefruit juice.
Serious illness that would interfere with study participation.
Hospitalization for any reason or therapy for serious illness within 14 days prior to study entry.
History of hypersensitivity to study drug or its formulation.
As determined by the investigator, a significant active or previous history of cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, or immunologic disease(s). This is inclusive of chronic illnesses such as hypertension, coronary artery disease, arthritis, diabetes, any chronic gastrointestinal conditions that may affect drug absorption, etc.
Breast-feeding.
Evidence of CNS infection or space occupying lesion by history or physical examination.
History of significant CNS disorder.
Prisoners or subjects who are compulsorily detained.
ABCB1 position 3435 C/T heterozygosity.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00729924

Locations


United States, Tennessee
Vanderbilt Therapeutics Clinical Research Site
Nashville, Tennessee, United States, 37204

Sponsors and Collaborators

Vanderbilt University

Investigators


Principal Investigator:	David W Haas, MD	Vanderbilt University

More Information

Publications:

Johnson DH, Sutherland D, Acosta EP, Erdem H, Richardson D, Haas DW. Genetic and non-genetic determinants of raltegravir penetration into cerebrospinal fluid: a single arm pharmacokinetic study. PLoS One. 2013 Dec 11;8(12):e82672. doi: 10.1371/journal.pone.0082672. eCollection 2013.


Responsible Party:	David Haas, Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00729924 History of Changes
Other Study ID Numbers:	080536
Study First Received:	August 4, 2008
Results First Received:	May 27, 2014
Last Updated:	March 2, 2015
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Vanderbilt University:


Raltegravir CSF ABCB1 SNP HIV/AIDS

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases	Raltegravir Potassium Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents HIV Integrase Inhibitors Integrase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2016